tbuckley/cabot-search huggingface dataset:
Genomic Basis of Adaptation to a Novel Precipitation Regime
Authors: Ahmed F Elfarargi, Elodie Gilbault, Nina Döring, Célia Neto, Andrea Fulgione, Andreas P M Weber, Olivier Loudet, Angela M Hancock
Journal: Molecular Biology and Evolution (2023)

Abstract Energy production and metabolism are intimately linked to ecological and environmental constraints across the tree of life. In plants, which depend on sunlight to produce energy, the link between primary metabolism and the environment is especially strong. By governing CO2 uptake for photosynthesis and transpiration, leaf pores, or stomata, couple energy metabolism to the environment and determine productivity and water-use efficiency (WUE). Although evolution is known to tune physiological traits to the local environment, we lack knowledge of the specific links between molecular and evolutionary mechanisms that shape this process in nature. Here, we investigate the evolution of stomatal conductance and WUE in an Arabidopsis population that colonized an island with a montane cloud scrubland ecosystem characterized by seasonal drought and fog-based precipitation. We find that stomatal conductance increases and WUE decreases in the colonizing population relative to its closest outgroup population from temperate North Africa. Genome-wide association mapping reveals a polygenic basis of trait variation, with a substantial contribution from a nonsynonymous single-nucleotide polymorphism in MAP KINASE 12 (MPK12 G53R), which explains 35% of the phenotypic variance in WUE in the island population. We reconstruct the spatially explicit evolutionary history of MPK12 53R on the island and find that this allele increased in frequency in the population due to positive selection as Arabidopsis expanded into the harsher regions of the island. Overall, these findings show how adaptation shaped quantitative eco-physiological traits in a new precipitation regime defined by low rainfall and high humidity.
Hospitalization Associated With Comorbid Psychiatric and Substance Use Disorders Among Adults With COVID-19 Treated in US Emergency Departments From April 2020 to August 2021
Authors: Lyna Z. Schieber, Christopher Dunphy, Richard A. Schieber, Barbara Lopes-Cardozo, Ramal Moonesinghe, Gery P. Guy
Journal: JAMA Psychiatry (2023)

During the COVID-19 pandemic, US emergency department (ED) visits for psychiatric disorders (PDs) and drug overdoses increased. Psychiatric disorders and substance use disorders (SUDs) independently increased the risk of COVID-19 hospitalization, yet their effect together is unknown.To assess how comorbid PD and SUD are associated with the probability of hospitalization among ED patients with COVID-19.This retrospective cross-sectional study analyzed discharge data for adults (age ≥18 years) with a COVID-19 diagnosis treated in 970 EDs and inpatient hospitals in the United States from April 2020 to August 2021.Any past diagnosis of (1) SUD from opioids, stimulants, alcohol, cannabis, cocaine, sedatives, or other substances and/or (2) PD, including attention-deficit/hyperactivity disorder (ADHD), anxiety, bipolar disorder, major depression, other mood disorder, posttraumatic stress disorder (PTSD), or schizophrenia.The main outcome was any hospitalization. Differences in probability of hospitalization were calculated to assess its association with both PD and SUD compared with PD alone, SUD alone, or neither condition.Of 1 274 219 ED patients with COVID-19 (mean [SD] age, 54.6 [19.1] years; 667 638 women [52.4%]), 18.6% had a PD (mean age, 59.0 years; 37.7% men), 4.6% had a SUD (mean age, 50.1 years; 61.7% men), and 2.3% had both (mean age, 50.4 years; 53.1% men). The most common PDs were anxiety (12.9%), major depression (9.8%), poly (≥2) PDs (6.4%), and schizophrenia (1.4%). The most common SUDs involved alcohol (2.1%), cannabis (1.3%), opioids (1.0%), and poly (≥2) SUDs (0.9%). Prevalence of SUD among patients with PTSD, schizophrenia, other mood disorder, or ADHD each exceeded 21%. Based on significant specific PD-SUD pairs (Q < .05), probability of hospitalization of those with both PD and SUD was higher than those with (1) neither condition by a weighted mean of 20 percentage points (range, 6 to 36; IQR, 16 to 25); (2) PD alone by 12 percentage points (range, -4 to 31; IQR, 8 to 16); and (3) SUD alone by 4 percentage points (range, -7 to 15; IQR, -2 to 7). Associations varied by types of PD and SUD. Substance use disorder was a stronger predictor of hospitalization than PD.This study found that patients with both PD and SUD had a greater probability of hospitalization, compared with those with either disorder alone or neither disorder. Substance use disorders appear to have a greater association than PDs with the probability of hospitalization. Overlooking possible coexisting PD and SUD in ED patients with COVID-19 can underestimate the likelihood of hospitalization. Screening and assessment of both conditions are needed.
A Standardized Approach for Collection of Objective Data to Support Outcome Determination for Late-Phase Tuberculosis Clinical Trials
Authors: Ekaterina V. Kurbatova, Patrick P. J. Phillips, Susan E. Dorman, Erin E. Sizemore, Kia E. Bryant, Anne E. Purfield, Jessica Ricaldi, Nicole E. Brown, John L. Johnson, Carole L. Wallis, Joseph P. Akol, Oksana Ocheretina, Nguyen Van Hung, Harriet Mayanja-Kizza, Madeleine Lourens, Rodney Dawson, Nguyen Viet Nhung, Samuel Pierre, Yeukai Musodza, Justin Shenje, Sharlaa Badal-Faesen, Stalz Charles Vilbrun, Ziyaad Waja, Lakshmi Peddareddy, Nigel A. Scott, Yan Yuan, Stefan V. Goldberg, Susan Swindells, Richard E. Chaisson, Payam Nahid
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

We developed a standardized method, possible poor treatment response (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary tuberculosis (TB).
High-Sensitivity Troponin T and I Among Pregnant Women in the US—The National Health and Nutrition Examination Survey, 1999-2004
Authors: Anum S. Minhas, Justin B. Echouffo-Tcheugui, Sui Zhang, Chiadi E. Ndumele, J. William McEvoy, Robert Christenson, Elizabeth Selvin
Journal: JAMA Cardiology (2023)

This cross-sectional study investigates the expected physiologic concentrations of high-sensitivity cardiac troponin in normal pregnancy.
CX<sub>3</sub>CR<sub>1</sub><sup>+</sup> Macrophage Facilitates the Resolution of Allergic Lung Inflammation via Interacting CCL26
Authors: Hyung-Geun Moon, Seung-jae Kim, Ki-Hyun Kim, Young-Mee Kim, Jalees Rehman, Hyun Lee, Yi-Chien Wu, Steve Seung-Young Lee, John W. Christman, Steven J. Ackerman, Minhyung Kim, Sungyoung You, Gye Young Park
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

The resolution of inflammation is an active process coordinated by mediators and immune cells to restore tissue homeostasis. However, the mechanisms for resolving eosinophilic allergic lung inflammation triggered by inhaled allergens have not been fully elucidated.
CMS Rule Cracks Down on Medicare Advantage Overpayments
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Comparing Kidney Transplant Rates and Outcomes Among Adults With and Without Intellectual and Developmental Disabilities
Authors: Brittany N. Hand, J. Madison Hyer, Austin Schenk, Alex Coyne, Daniel Gilmore, Lauren Wang, Aslam Ejaz
Journal: JAMA Surgery (2023)

Improving equity in organ transplant access for people with intellectual and developmental disabilities (IDD) is a topic of social discourse in mainstream media, state legislation, and national legislation. However, few studies have compared evaluation rates, transplant rates, and outcomes among adults with and without IDD.To compare rates of kidney transplant and transplant-specific outcomes between propensity-score matched groups of adults with end-stage kidney disease (ESKD [also referred to as end-stage renal disease (ESRD)]) with and without co-occurring IDD.This retrospective cohort study included all Medicare inpatient and outpatient standard analytical files from 2013 through 2020. A total of 1 413 655 adult Medicare beneficiaries with ESKD were identified. Propensity-score matching was used to balance cohorts based on age, sex, race, follow-up duration, and Charlson Comorbidity Index. The matched cohorts consisted of 21 384 adults with ESKD (10 692 of whom had IDD) and 1258 kidney transplant recipients (629 of whom had IDD). Data were analyzed between June 1, 2022, and August 1, 2022.IDD.Evaluation for kidney transplant, receipt of kidney transplant, perioperative complications, readmission, mortality, graft rejection, and graft failure.Of the 21 384 propensity-score matched adults with ESKD, the median (IQR) age was 55 (43-65) years, 39.2% were male, 27.4% were Black, 64.1% were White, and 8.5% identified as another race or ethnicity. After propensity score matching within the ESKD cohort, 633 patients with IDD (5.9%) received a kidney transplant compared with 1367 of adults without IDD (12.8%). Adults with IDD were 54% less likely than matched peers without IDD to be evaluated for transplant (odds ratio, 0.46; 95% CI, 0.43-0.50) and 62% less likely to receive a kidney transplant (odds ratio, 0.38; 95% CI, 0.34-0.42). Among matched cohorts of kidney transplant recipients, rates of perioperative complications, readmission, and graft failure were similar for adults with and without IDD.Using the largest cohort of adult kidney transplant recipients with IDD to date, the study team found that rates of evaluation and transplant were lower despite yielding equivalent outcomes. These data support consideration of adults with IDD for kidney transplant and underscore the urgent need for antidiscrimination initiatives to promote the receipt of equitable care for this population.
Ribosome dysfunction underlies SLFN14-related thrombocytopenia
Authors: Fabienne Ver Donck, Kato Ramaekers, Chantal Thys, Christine Van Laer, Kathelijne Peerlinck, Chris van Geet, Koji Eto, Veerle Labarque, Kathleen Freson
Journal: Blood (2023)

Pathogenic missense variants in SLFN14, which encodes an RNA endoribonuclease protein that regulates rRNA degradation, are known to cause inherited thrombocytopenia with impaired platelet aggregation and ATP secretion. Despite rather mild laboratory defects, these patients display an obvious bleeding phenotype. The function of SLFN14 in megakaryocyte (MK) and platelet biology is unknown. This study aims to model the disease in the immortalized megakaryocyte cell line imMKCL and characterize the platelet transcriptome in patients with a SLFN14 K219N variant. MK derived from heterozygous and homozygous SLFN14 K219N imMKCL and stem cells of blood from patients mainly presented with a defect in proplatelet formation and mitochondrial organization. SLFN14 defective platelets and mature MK showed signs of rRNA degradation while this was absent in undifferentiated imMKCL cells and granulocytes. Total platelet RNA was sequenced for two patients and 19 healthy controls. Differential gene expression analysis yielded a total of 2999 and 2888 significantly (|log2FC|&amp;gt;1, FDR&amp;lt;0.05) up- and downregulated genes, respectively. Remarkably, these downregulated genes were not enriched for any biological pathway while upregulated genes were enriched for pathways involved in (mitochondrial) translation and transcription with a significant upregulation of 134 ribosomal protein genes (RPG). Upregulation of (M)RPG through increased mTORC1 signaling in SLFN14 K219N MK seems to be a compensatory response to rRNA degradation. Indeed, mTORC1 inhibition with rapamycin resulted in further enhanced rRNA degradation in SLFN14 K219N MK. Taken together, our study indicates dysregulation of mTORC1 coordinated ribosomal biogenesis as the disease mechanism for SLFN14-related thrombocytopenia.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2023)

Mutant KRAS Promotes Innate Immunoevasion through CD47Although KRAS mutations are one of the most common recurrent alterations, treatments are lacking for the majority of KRAS mutant tumors.Mutant KRAS can promote evasion of the adaptative immune response; however, its influence on the innate response is unclear.Hu and colleagues, utilizing both in vitro and in vivo nonsmall cell lung cancer models and patient samples, demonstrated that mutant KRAS drives innate immunoevasion through upregulation of cluster of differentiation 47 (CD47), which acts as a "don't eat me" signal.CD47 prevented macrophage-dependent phagocytosis and promoted tumorigenesis.Conversely, mutant KRAS inhibition decreased CD47 expression and restored phagocytosis and innate immunity.
Racial disparities in diagnostic evaluation of uterine cancer among Medicaid beneficiaries
Authors: Xiao Xu, Ling Chen, Marcella Nunez-Smith, Mitchell Clark, Jason D Wright
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background To inform reasons contributing to Black-White disparity in early diagnosis of uterine cancer, we compared the quality of diagnostic evaluation received by Black vs White patients with abnormal uterine bleeding (AUB) ultimately diagnosed with uterine cancer. Methods Using 2008-2019 MarketScan Multi-State Medicaid Database, we identified Black (n = 858) and White (n = 1749) patients with uterine cancer presenting with AUB. Quality of diagnostic evaluation was measured by delayed diagnosis (&amp;gt;1 year after AUB reporting), not receiving guideline-recommended diagnostic procedures, delayed time to first diagnostic procedure (&amp;gt;2 months after AUB reporting), number of diagnostic procedures received, and number of evaluation and management visits for AUB. The association between race and quality indicators was examined by multivariable regressions adjusting for patient characteristics. Results Black patients were more likely than White patients to experience delayed diagnosis (11.3% vs 8.3%, P = .01; adjusted odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.27 to 2.29) or to not receive guideline-recommended diagnostic procedures (10.1% vs 5.0%, P &amp;lt; .001; adjusted OR = 1.94, 95% CI = 1.40 to 2.68). Even when they did receive recommended diagnostic procedures, Black patients were more likely than White patients to experience delay in time to the first diagnostic procedure (adjusted OR = 1.46, 95% CI = 1.09 to 1.97). In addition, Black patients underwent more evaluation and management visits for AUB before getting diagnosed compared with White patients (adjusted mean ratio = 1.13, 95% CI = 1.04 to 1.23). Conclusions Black and White patients with uterine cancer differed in the quality of diagnostic evaluation received. Improving equity in this area may help reduce Black-White disparity in stage at diagnosis.
Phase II trials in the era of glioblastoma immunotherapy: New mechanisms of action, familiar challenges in trial design and tumor response assessment
Authors: Stephen J Bagley
Journal: Neuro-Oncology (2023)

Journal Article Phase II trials in the era of glioblastoma immunotherapy: New mechanisms of action, familiar challenges in trial design and tumor response assessment Get access Stephen J Bagley Stephen J Bagley Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA Corresponding Author: Stephen J. Bagley, MD, MSCE, Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 10th Floor Perelman Center South Pavilion, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA (sbagley@pennmedicine.upenn.edu). https://orcid.org/0000-0002-7117-0539 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 6, June 2023, Pages 1098–1099, https://doi.org/10.1093/neuonc/noad043 Published: 15 February 2023 Article history Published: 15 February 2023 Corrected and typeset: 07 March 2023
LGR4: A New Receptor Member in Endocrine and Metabolic Diseases
Authors: Ningning Zhang, Mingyang Yuan, Jiqiu Wang
Journal: Endocrine Reviews (2023)

Abstract Classic hormone membrane receptors, such as leucine-rich repeat-containing G protein–coupled receptor (LGR) 1 (follicle-stimulating hormone receptor), LGR2 (luteinizing hormone receptor), and LGR3 (thyrotropin receptor), are crucial in endocrinology and metabolism, and the identification of new receptors can advance this field. LGR4 is a new member of this G protein–coupled receptor family and shows ways of expression and function similar to those of LGR1/2/3. Several recent studies have reported that, unlike LGR5/6, LGR4 plays essential roles in endocrine and metabolic diseases, including hypothalamic–gonadal axis defects, mammary gland dysplasia, osteoporosis, cardiometabolic diseases, and obesity. An inactivating mutation p.R126X in LGR4 leads to osteoporosis, electrolyte disturbance, abnormal sex hormone levels, and weight loss, whereas an activating mutation p.A750T is associated with bone mineral density, insulin resistance, and adiposity. Though several paracrine ligands are known to act on LGR4, the endocrine ligands of LGR4 remain poorly defined. In this review, we highlight LGR4 dysfunction in clinical diseases, animal models, and pathophysiological changes, discuss their known ligands and downstream signaling pathways, and identify unresolved questions and future perspectives of this new receptor.
High drug prices are not justified by industry’s spending on research and development
Authors: Aris Angelis, Roman Polyakov, Olivier J Wouters, Els Torreele, Martin McKee
Journal: BMJ (2023)

From 1999 to 2018, the world's 15 largest biopharmaceutical companies spent more on selling, general, and administrative activities ($2.2 trillion) than on research and development ($1.4 trillion), although the gap narrowed over time.• Most of these companies also spent more on share buybacks and dividends than on research and development.• Most new medicines developed during this period offered little or no added benefit over existing treatments, making it difficult to sustain the argument that high prices are needed for valuable innovation.• The biopharmaceutical industry could generate more medically valuable innovation with existing resources using affordable pricing, but government action would be needed along the lifecycle of new medicines.
Health and nutrition claims for infant formula: international cross sectional survey
Authors: Ka Yan Cheung, Loukia Petrou, Bartosz Helfer, Erika Porubayeva, Elena Dolgikh, Sana Ali, Insaf Ali, Lindsay Archibald-Durham, Meredith (Merilee) Brockway, Polina Bugaeva, Rishma Chooniedass, Pasquale Comberiati, Erika Cortés-Macías, Sofia D’Elios, Gavriela Feketea, Peter Hsu, Musa Abubakar Kana, Tatiana Kriulina, Yuzuka Kunii, Comfort Madaki, Rihab Omer, Diego Peroni, Jana Prokofiev, Melanie Rae Simpson, Naoki Shimojo, Linda P Siziba, Jon Genuneit, Sohini Thakor, Marium Waris, Quan Yuan, Sadia Zaman, Bridget E Young, Brighid Bugos, Matthew Greenhawt, Michael E Levin, Jonathan Zheng, Robert J Boyle, Daniel Munblit
Journal: BMJ (2023)

To review available health and nutrition claims for infant formula products in multiple countries and to evaluate the validity of the evidence used for substantiation of claims.
VIS Atlas: A Database of Virus Integration Sites in Human Genome from NGS Data to Explore Integration Patterns
Authors: Ye Chen, Yuyan Wang, Ping Zhou, Hao Huang, Rui Li, Zhen Zeng, Zifeng Cui, Rui Tian, Zhuang Jin, Jiashuo Liu, Zhaoyue Huang, Lifang Li, Zheying Huang, Xun Tian, Meiying Yu, Zheng Hu
Journal: Genomics Proteomics & Bioinformatics (2023)

Integration of oncogenic DNA viruses into the human genome is a key step in most virus-induced carcinogenesis. Here, we constructed a virus integration site (VIS) Atlas database, an extensive collection of integration breakpoints for three most prevalent oncoviruses, human papillomavirus, hepatitis B virus, and Epstein-Barr virus based on the next-generation sequencing (NGS) data, literature, and experimental data. There are 63,179 breakpoints and 47,411 junctional sequences with full annotations deposited in the VIS Atlas database, comprising 47 virus genotypes and 17 disease types. The VIS Atlas database provides (1) a genome browser for NGS breakpoint quality check, visualization of VISs, and the local genomic context; (2) a novel platform to discover integration patterns; and (3) a statistics interface for a comprehensive investigation of genotype-specific integration features. Data collected in the VIS Atlas aid to provide insights into virus pathogenic mechanisms and the development of novel antitumor drugs. The VIS Atlas database is available at https://www.vis-atlas.tech/.
Clinical phage microbiology: a narrative summary
Authors: Gina A Suh, Robin Patel
Journal: Clinical Microbiology and Infection (2023)

Although phage therapy has been in existence for a century, a recent resurgence in interest has occurred because of the continued emergence of antimicrobial resistance and the rising use of indwelling medical devices, resulting in biofilm-associated infections, for which conventional antibiotics are of limited use. Despite this, the clinical successes have been inconsistent because of multiple reasons, including (1) the narrow host range of phages, (2) challenges with concentrating phages at the site of infection, (3) development of resistance of bacteria to phages and (4) immune neutralization. Microbiologic assays have the potential to help guide the course of clinical therapy and improve outcomes. Methods developed decades ago remain the mainstay of phage diagnostics and recently, newer diagnostics are closing the gap needed to further advance clinical phage therapy.To review the current state of clinical phage microbiology and identify gaps.A PubMed search was performed using the terms "phage microbiology", "phage susceptibility test", "phage host range", "phage biofilm", and "phage therapeutic monitoring".Phage susceptibility testing, biofilm assays, phage-antibiotic combination testing, therapeutic drug monitoring, and immune monitoring assays are the current foundation for clinical phage diagnostics. Standardization of these assays and better understanding as to if and how they should be used in terms of clinical management of patients receiving phage therapy is needed.A substantial gap between in vitro studies and in vivo outcomes indicates that further work is needed in phage pharmacokinetics to accurately assay phage particles at the site of infection; recapitulate in vivo biofilm; capture the complex interactions between phages and antibiotics, phages and their target bacteria, among phages in a cocktail, and with the superhost immune system.